ORIGINAL RESEARCH article
Front. Immunol.
Sec. Nutritional Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1649327
This article is part of the Research TopicHealth Effects of Natural Compounds from PlantsView all 13 articles
Isorhamnetin attenuates renal interstitial fibrosis by targeting TWEAK/Fn14-mediated epithelial-mesenchymal transition
Provisionally accepted
Yaping Chen1Wenchuan Luo1Hongxiang Guan2Zixin Chen1Zhihui Chen1Lijuan Xiao1
Wen Xu1Mei Huang1Ya Lin1
Yuqin Zhang1Weihua Peng3
Lihong Nan1*- 1Fujian University of Traditional Chinese Medicine, Fuzhou, China
- 2Fuzhou Traditional Chinese Medicine Hospital, Fuzhou, China
- 3900th Hospital of the People's Liberation Army Joint Logistic Support Force, Fuzhou, China
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Introduction: Isorhamnetin (ISO), a prominent active compound found in the fruits of Hippophae rhamnoides L., exhibits various pharmacological activities. Recent studies have demonstrated that ISO possesses significant renoprotective effect. Nevertheless, the specific targets and mechanisms through which ISO exerts its effects against renal interstitial fibrosis (RIF) remain insufficiently explored. This study aimed to explore the protective effects of ISO regulating EMT and reliving RIF and elucidate the underlying molecular mechanisms involved in the TWEAK/Fn14 pathway. Methods: We explored the potential effects and mechanisms of ISO on RIF by using both in vitro EMT models of a TGF-β-induced human proximal tubular cell line (HK-2) and an in vivo unilateral ureteral obstruction (UUO) model. The potential mechanism of TWEAK/Fn14 pathway involving protective action of ISO on renal tubules was explored by surface plasmon resonance (SPR) analysis, and Fn14 overexpression on UUO rats. Results: Our findings reveal that ISO can enhance cell morphology and effectively inhibit the migration ability of TGF-β-induced HK-2 cells. ISO also improved renal dysfunction, reduced tubular damage induced by UUO, significantly increasing Ecadherin expression, decreasing α-SMA and the main component of the ECM (Col III and FN), in vivo. The results show that ISO demonstrates potent inhibition of EMT in renal tubular epithelial cells, both in vivo and in vitro. The specific interaction between ISO and Fn14 was confirmed by SPR analysis. Overexpression of Fn14 counteracts the renoprotective effects of ISO, mitigating its influence on the inactivation of the TWEAK/Fn14 signaling pathway.Conclusions: These confirmed that ISO inhibits the EMT of renal tubular epithelial cells by suppressing the TWEAK/Fn14 signalling pathway.
Keywords: Isorhamnetin, Renal interstitial fibrosis, epithelial mesenchymal transition, TWEAK, Fn14 Abbreviations: EMT, epithelial mesenchymal transition, ECM, extracellular matrix, RIF, renal interstitial fibrosis, ISO, isorhamnetin
Received: 18 Jun 2025; Accepted: 18 Aug 2025.
Copyright: © 2025 Chen, Luo, Guan, Chen, Chen, Xiao, Xu, Huang, Lin, Zhang, Peng and Nan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lihong Nan, Fujian University of Traditional Chinese Medicine, Fuzhou, China
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